DIVERSITY OF CTL EPITOPES AND CHLAMYDIA

我们以前已经发现，在沙眼衣原体感染过程中，能够特异性裂解衣原体感染细胞的细胞毒性T淋巴细胞(CTL)被激活。将培养的CTL过继转移到感染的小鼠体内，对沙眼衣原体具有保护作用。这项建议中的实验使用生化方法来鉴定引起CTL反应的衣原体抗原。这项建议中确定的抗原将在使用重组炭疽毒素递送系统的疫苗策略中测试它们产生保护性免疫的能力。该项目将继续依赖于其他核心和项目。还提出了初步实验，以解决这些抗原中的哪些在人类感染期间被识别。我们设想，这里描述的疫苗策略将被纳入旨在刺激免疫系统多个手臂的多价疫苗中。开发一种有效的人类疫苗将减少这些感染的发病率，这些感染是造成全球大量发病率的原因。这些实验不仅将加深我们对CTL在抗衣原体免疫中的重要性的理解，而且还将提供对细胞内、空泡病原体的免疫识别的更好的理解。由于MHC-I类分子上的抗原通常存在于宿主细胞的细胞质中，因此识别逃离空泡室并被加工成MHC-I类分子呈递给CTL的抗原亚集将进一步加深我们对这些非常复杂的宿主细胞-病原体相互作用的理解。已鉴定的这类抗原也可能与其他细胞内空泡病原体有同源关系，包括沙门氏菌、军团菌和分枝杆菌。

We have found previously that cytotoxic T-lymphocytes (CTL) capable of specific lysis of Chlamydia infected cells are primed during infection with C. trachomatis. Adoptive transfer of cultured CTL into an infected mouse affords protection against C. trachomatis. The experiments in this proposal use a biochemical approach to identify Chlamydia antigens which give rise to the response by CTL. The antigens identified in this proposal will be tested for their ability to engender protective immunity in a vaccine strategy using a recombinant anthrax toxin delivery system. This project will continue to rely on other cores and projects. Initial experiments are also proposed that will address which of these antigensare recognized during human infection. We envision that the vaccine strategy described here would be incorporated into a multivalent vaccine designed to stimulate multiple arms of the immune system. Development of an effective human vaccine would reduce the incidence these infections that are responsible for a great deal of worldwide morbidity. These experiments will not only further our understanding of the importance of CTL in immunity against Chlamydia, but also will provide better understanding of immune recognition by intracellular, vacuolar pathogens in general. Because antigens presented on MHC class I molecules generally are found in the cytoplasm of host cells, identification of a subset of antigens which escape the vacuolar compartment to be processed for presentation on MHC class I molecules to CTL will further our understanding of these very complex host cell-pathogen interactions. The class of antigens identified may also have homologues in other intracellular vacuolar pathogens including Salmonella, Legionella, and Mycobacterium.